Characterization of mutations in streptomycin-resistant Mycobacterium tuberculosis clinical isolates in the area of Barcelona

Objectives To determine the proportion and type of mutations in Mycobacterium tuberculosis isolates resistant to streptomycin, and their relationship with the level of resistance and with the epidemiological molecular pattern of the isolates. Methods Sixty-nine streptomycin-resistant isolates from a...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2010-11, Vol.65 (11), p.2341-2346
Main Authors: Tudó, Griselda, Rey, Emma, Borrell, Sònia, Alcaide, Fernando, Codina, Gemma, Coll, Pere, Martín-Casabona, Núria, Montemayor, Michel, Moure, Raquel, Orcau, Àngels, Salvadó, Margarita, Vicente, Eva, González-Martín, Julià
Format: Article
Language:English
Subjects:
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antitubercular Agents - pharmacology
Bacteria
Bacterial diseases
Bacterial Typing Techniques
Biological and medical sciences
DNA Fingerprinting
DNA Transposable Elements
DNA, Bacterial - genetics
Drug resistance
Drug Resistance, Bacterial
Epidemiology
Genes
Human bacterial diseases
Humans
Infectious diseases
M. tuberculosis
Medical sciences
Microbial Sensitivity Tests
Mutation
Mutation, Missense
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - isolation & purification
Pharmacology. Drug treatments
Polymorphism
Ribosomal Proteins - genetics
rpsL
rrs
Spain
Streptomycin - pharmacology
streptomycin resistance
Tuberculosis
Tuberculosis - microbiology
Tuberculosis and atypical mycobacterial infections
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Summary:Objectives To determine the proportion and type of mutations in Mycobacterium tuberculosis isolates resistant to streptomycin, and their relationship with the level of resistance and with the epidemiological molecular pattern of the isolates. Methods Sixty-nine streptomycin-resistant isolates from a M. tuberculosis strain collection (1995–2005) from Barcelona were studied. The MIC of streptomycin for each isolate was determined using the proportions method with Middlebrook 7H11 medium. The entire rpsL gene and two specific fragments of the rrs gene (the 530 loop and the 912 region) were sequenced. IS6110-restriction fragment length polymorphism and spoligotyping were performed in each isolate. Results Twenty-six (26/69, 37.7%) streptomycin-resistant isolates presented a mutation in either the rpsL gene and/or the rrs530 loop, with no mutation in the rrs912 region. Seventeen (24.6%) isolates showed rpsL mutations (codons 43 and 88) associated with high MIC levels. Nine (13.0%) isolates had alterations in the rrs gene (A513T, A513C and C516T). Nineteen isolates (19/64, 29.7%) were classified into seven clusters (containing 2–5 isolates per cluster). Nineteen different spoligotype patterns were found. All the LAM3 spoligotype isolates (10/67, 14.9%) were associated with a C491T change in the rrs gene, being also observed in all LAM3 streptomycin-susceptible isolates. Conclusions Mutations in the rpsL and rrs genes were detected in 37.7% of streptomycin-resistant M. tuberculosis isolates. High-level resistance was associated with mutations in the rpsL gene, whereas wild-type isolates showed low MIC levels. The presence of the C491T substitution in the rrs gene in streptomycin-susceptible and -resistant isolates demonstrates that this change is an epidemiological marker associated with LAM3 sublineage.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkq322